Damage or destruction of the blood supply to a region of living tissue quickly leads to compromised tissue. One of the critical functions of an adequate blood supply is the provision of dissolved gases to the site, such as oxygen. For example, wounds to bodily tissues are accompanied by damage or destruction of the natural blood supply that transports oxygen and nutrients that are necessary to support the healing process. Measurements have shown that the tissue oxygen tension within the wound and surrounding damaged tissues is substantially lower than the normal blood vascular oxygen tension. Whereas the blood vascular oxygen level of 80 to 100 mm Hg is considered normal, the wound environment may have as little as 3 to 30 mm Hg of oxygen. Research has shown that a level of 30 mm Hg or less is insufficient to support the processes of wound repair.
Oxygen has been shown to have therapeutic effect in healing of wounds and in preventing growth of anaerobic bacteria etc. While oxygen may be available from air for direct dissolution into wound fluids, availability of topically dissolved oxygen is preferred as it raises oxygen tension to desired levels more quickly, thus accelerating its benefits in wound healing.
Many approaches have been used in an effort to increase the amount of oxygen delivered to compromised tissues. For example, U.S. Pat. No. 5,407,685 describes a device for generating oxygen when the device was applied to a wound. The device disclosed is a bilayered device where each layer contains a reactant that mixes and generates oxygen once exudate or other bodily-derived material activates the reaction. U.S. Pat. No. 5,736,582 describes the generation of oxygen from hydrogen peroxide for release at or near the skin surface. U.S. Pat. No. 5,855,570 similarly uses an electrochemical reaction to convert oxygen in air to a peroxide or other reactive form of oxygen for delivery to the wound environment. U.S. Pat. No. 5,792,090 uses a reservoir that contained hydrogen peroxide and a catalyst in a device in contact with the wound, such as a hydrogel or polymeric foam. Another approach was disclosed in U.S. Pat. No. 5,086,620 in which pure gaseous oxygen was dispersed by sonic energy into a liquid matrix that was then solidified by cooling to encapsulate the oxygen in minute bubbles.
These devices represent improvements in the delivery of topical oxygen to the wound environment over conventional hyperbaric chambers. However, each carries significant limitations that have restricted the broad adaptation of the technology of topical oxygenation for care of compromised tissues. Previously described devices do not have a known concentration of oxygen and cannot function independently of atmospheric pressures or temperature to achieve effective oxygen distribution. In addition, the dependence upon activation by body-derived agents is unpredictable so as to make such devices impractical. Other devices are expensive to produce and require specialized equipment. Such devices cannot be used in the production of cold set polymers that are often used for the construction of medical devices used for compromised tissue care.
One particularly useful approach to delivering oxygen to a wound is described in U.S. Pat. No. 7,160,553 for “Matrix for Oxygen Delivery to Compromised Tissues”, issued Jan. 9, 2009 to Gibbins et al. That patent describes a closed cell oxygen-containing foam dressing based on polyacrylamide. The closed cell oxygen foam dressing is biocompatible and laboratory tests have shown the dressing is able to increase oxygen tension in saline as high as 200 mm Hg. The foam dressing has high capacity for fluid absorption (up to 10 grams fluid per gram of foam) and has no adverse cytotoxicity. The foam dressing is suited for application in surface wounds for sustained delivery of topically dissolved oxygen for 72 hours. While the closed cell oxygen foam dressing is biocompatible, it is not biosorbable. (i.e., it is not suitable for use inside the human body).
In a variety of surgical situations, especially those involving internal surgeries, there is a need for a sheet dressing that may act as a spacer, help heal surgical incisions faster by supplying topically dissolved oxygen and doing away with the need for removal of dressing from the surgical site due to its intrinsic biosorbable property. There are biosorbable collagen sponges and some polyurethane base biosorbable dressings known in published literature. However, none are able to provide topically dissolved oxygen in addition to be biocompatible and biosorbable.
The Gibbins et al. patent describes the use of gelatin, a biodegradable material, for making a non-polyacrylate based oxygen foam dressing using a sodium carbonate-hydrogen peroxide system which resulted in a pliable foam material with oxygen gas trapped in bubbles within the dressing. However, such a dressing is not cross-linked (unlike its polyacrylate counterpart) and would lack wet strength. Such a deficiency makes handling of the dressing during manufacturing and in use difficult and impractical.
The wet strength of the gelatin gel sheets could be improved by cross-linking them with the help of glutaraldehyde or formaldehyde. While these two reagents are the most commonly used in gelatin cross-linking, they are unsuitable for making cross-linked gelatin biosorbable oxygen foam dressings because they are toxic. Any residue of these chemicals in the dressings is highly undesirable.
Accordingly, there is a need for a biosorbable closed cell oxygen foam that has wet strength and is practical to manufacture and handle. There is also a need for a practical and economical method of manufacturing such a biosorbable closed cell oxygen foam having wet strength properties. A need also exists for a sheet dressing that may act as a spacer, help heal surgical incisions faster by supplying topically dissolved oxygen and doing away with the need for removal of the dressing from the surgical site. Moreover, there is a need for methods of using a sheet dressing as a spacer to help heal surgical incisions faster by supplying topically dissolved oxygen and doing away with the need for removal of the dressing from the surgical site. Methods and compositions are needed that can provide oxygen to a surgical site and delivery of active agents with the need for removal of a dressing from the surgical site.